Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate

Colin Rickman, Deborah A Archer, Frederic A Meunier, Molly Craxton, Mitsunori Fukuda, Robert D Burgoyne, Bazbek Davletov

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Synaptotagmins are membrane proteins that possess tandem C2 domains and play an important role in regulated membrane fusion in metazoan organisms. Here we show that both synaptotagmins I and II, the two major neuronal isoforms, can interact with the syntaxin/synaptosomal-associated protein of 25 kDa (SNAP-25) dimer, the immediate precursor of the soluble NSF attachment protein receptor (SNARE) fusion complex. A stretch of basic amino acids highly conserved throughout the animal kingdom is responsible for this calcium-independent interaction. Inositol hexakisphosphate modulates synaptotagmin coupling to the syntaxin/SNAP-25 dimer, which is mirrored by changes in chromaffin cell exocytosis. Our results shed new light on the functional importance of the conserved polybasic synaptotagmin motif, suggesting that synaptotagmin interacts with the t-SNARE dimer to up-regulate the probability of SNARE-mediated membrane fusion.
Original languageEnglish
Pages (from-to)12574-12579
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number13
DOIs
Publication statusPublished - 26 Mar 2004

Keywords

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Brain
  • Calcium
  • Calcium-Binding Proteins
  • Catecholamines
  • Cell Membrane
  • Chromaffin Cells
  • Cloning, Molecular
  • Dimerization
  • Dose-Response Relationship, Drug
  • Evolution, Molecular
  • Exocytosis
  • Glutathione Transferase
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Membrane Glycoproteins
  • Membrane Proteins
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Neurons
  • Phytic Acid
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Qa-SNARE Proteins
  • RNA, Messenger
  • Rats
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synaptosomal-Associated Protein 25
  • Synaptotagmins
  • Time Factors

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